Method of making a prolonged action medicinal tablet



Feb. 28, 1956 HERMEUN 2,736,682

METHOD OF MAKING A PROLONGED ACTION MEDICINAL TABLET Original Filed Nov. 13, 1950 INVENTOR. VBI$TOR M. HERMELIN United States Patent MAKING A PROLUNGED ACTION MEDICINAL TABLET Victor M. Hermelin, Olivette, Mo.

6 Claims. (Cl. 167-82) NHSTHOD OF This invention relates in general to certain new and useful improvements in pharmaceutical preparations and, more particularly, to a unique type of sedative tablet. This present application is a continuation of application Serial No. 195,369, filed November 13, 1950, now abandoned.

The medical profession frequently has need for a type of sedative tablet or hypnotic preparation which can be administered to the patient for purposes of achieving a very quick narcosis or hypnotic effect and will also maintain such effect over a prolonged period of time. Unfortunately, the quick-acting sedatives and hypnotics usually produce a sedated or narcotized condition of relatively short duration and are administered in comparatively light doses in order to avoid toxic reactions or other effects which would be harmful to the patient. At the present time, there is no sedative drug which is capable of producing both quick speedy sedation and prolonged, but harmless, narcosis and which is even relatively safe if chewed up by the patient during administration.

It is the primary object of the present invention, therefore, to provide a type of pharmaceutical preparation which, in a single tablet, is capable of producing both a quick initial sedation and a prolonged narcosis which will last over any desired or predetermined period of time.

It is another object of the present invention to provide a pharmaceutical tablet having the combined effects of prompt sedation and prolonged sedative effect, which tablet is simple to administer and relatively economical in cost of preparation and will not be harmful if accidentally chewed up by the patient during administration.

With the above and other objects in view, my invention resides in the novel features of form, construction, arrangernent, and combination of parts presently described and pointed out in the claims.

In the accompanying drawing the figure is a transverse sectional view of a sedative tablet constructed in accordance with and embodying the present invention.

Broadly speaking, the present invention resides in the discovery that it is possible to form a tablet having a central slug or core consisting of protectively coated particles of a sedative drug which will produce a prolonged gentle sedative effect or narcosis upon the patient and an outer envelope formed of a drug which is capable of producing a very quick or almost immediate sedative or soporific effect upon the patient. The inner or core portion and the outer envelope are separated from each other by a coating or enveloping layer which will resist the action of the fluids in the stomach and intestines for a predetermined period of time. The outer envelope containing the quick acting drug is preferably coated or encased in the usual readily soluble sugar coating capable of being dissolved in the stomach juices. The intermedi ate coating is furthermore uniquely compounded so as to prevent any diffusion between the inner and outer portions of the tablet either during storage or while in the stomach of the patient during the time in which the outer envelope is being dissolved and rendered effective.

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Referring now inmore detail and by reference characters to the drawing, which illustrates a practical embodiment of the present invention, A designates a dual-effect tablet comprising a central spherical slug or core 1 formed by placing powdered phenobarbital in a mixer and adding confectioners glaze, stearic acid, and castor oil to form a dough-like mixture which is spread on trays to dry and, when dry, is comminuted to pass a sixteen mesh screen. The granular phenobarbital mixture is then again wetted down with an additional quantity of the glaze-stearic acidcastor oil mixture and again dried and screened. This granulated mixture of coated particles is then compressed in a conventional tableting machine to form the slugs or cores 1.

A suitable quantity of slugs or cores 1 are placed in a conventional coating pan and a quantity of the glazestearic acid-castor oil mixture poured thereinto in a sufficient quantity to wet the entire surface of the slugs or I cores 1. Thereupon, kaolin is dusted into the coating pan until the liquid film has been completely dried up. Thereupon, another similar quantity of the glaze-stearic acid-caster oil mixture is poured into the coating pan until the cores 1 are again wetted with another or second thin film and again a suitable quantity of dry kaolin is dusted into the coating pan to be taken up by the liquid film. This process is repeated a number of times until a substantially thick dense enclosing layer 2 is built up around the core. The coated cores 1 are thereupon removed from the coating pan and allowed to dry for a period of approximately twenty-four hours during which period the layer 2 becomes firmly set and hardened.

Thereupon, the coated cores 1 are again placed in a coating pan and a simple syrup USP is slowly poured into the coating pan until a moist film is formed thereon and sodium pentobarbital is dusted into the pan until the moist film is dry. When the first layer is dry, a second and third layers are applied in like manner until the desired layer 3 is finally built up which contains the desired dosage. As this process is being carried on, care must be observed to remove a representative sample of the tablets A at fairly frequent intervals as the layer 3 is being built up because it is important to ascertain that the dosage is maintained within fairly accurate and precise limits. it the dosage is not suflicient, additional applications can be made until the right dosage is obtained on the tablets.

It has been found by extensive experimentation that it is entirely possible and feasible. to build up an outer shell or envelope 3 consisting of sodium pentobarbital or a similar quick-acting hypnotic drug around the coated core 1. It has also been found in this connection that by applying the sodium pentobarbital or similar material slowly and with reasonably frequent sampling an extremely accurate tablet can be produced. The spherical form lends itself uniquely to this process since such shapes have the highly desirable property of building up extremely uniform quantities of films or coatings as they are rotated in coating pans.

When the'layer 3 is built up to the desired thickness, the tablets A may, ifdesired/be coated with a conventional sugar-coating 4 which may be colored to any desirable shade depending upon taste or desires of the druggist or purchasing public.

When the tablet A is administered, the outer sugarcoating 4 and the sodium pentobarbital layer will dissolve quite rapidly in the fluids of the patients stomach. A rapid sedative or hypnotic effect will thus be achieved so that the patient will come under influence of the drug within a. matter of ten to fifteen minutes after administration and depending upon the susceptibility of the patient such effect will continue for a substantial period of time, say, for example, three hours. Meanwhile, the tablet may remain in the stomach or may, as a result of the normal peristaltic movement of the stomach, pass into the upper portion of the intestine or large bowel. The travel of stomach contents into the intestines may take place in two to six hours and is a very inexact process. \Vith tablets of the present invention, however, this makes no difference because the coating will disintegrate at the end of the time period for which it is designed whether in the stomach or intestines. This coating, once it begins to be acted upon, does not dissolve immediately, but allows the stomach and intestinal fluids to permeate through the coating and attack the core 1. The core 1, consisting of coated particles, will gradually go into solution and will dialize outwardly through the wetted coating 2 gradually going into the patients system. It has been found that the core 1 will require approximately one hour to disintegrate completely by this process, thus the slow long-acting drug of the core will go into solution very gradually and will maintain its hypnotic effect over a relatively long period of time.

It will, of course, be understood in this connection that the length of time during which the patient will be narcotized will depend upon the amount of hypnotic drug which has been incorporated into the core 1. It has been found that by use of the unique type of coating 2 and a core 1, consisting of coated particles, the long-acting drug will be absorbed into the patients system rather slowly and will thus produce a desirable effect over a much longer period of time with a given dosage than has heretofore been obtained under conventional methods of administration. This makes it possible to keep thepatient narcotized over longer periods of time with smaller quantities of the drug.

Example I Core: Gr./ tablet Phenobarbital 1 Lactose /2 Outer layer: Sodium phenobarbital 1 Appropriate amounts of the above ingredients to form approximately a 70 pound batch in the stated proportions are thoroughly mixed. A suitable quantity of the abovementioned glaze-stearic acid-castor oil mixture is prepared by mixing and thoroughly stirring the following ingredients in the following proportions:

Glaze gallons 1 Stearic acid pounds 2 Castor oil ounces 8 One-half gallon of the above glaze-stearic acid-castor oil mixture is added and thoroughly intermixed with the dry phenobarbital-lactose mixture and spread on trays to dry. When dry, this mixture is comminuted to pass a sixteen mesh screen. This granular mixture is then wetted down with one-fourth gallon of the above glaze-stearic acidcastor oil mixture and again dried and screened to form a I granulated mixture consisting of particles of the medication which are externally coated with the dried glazestearic acid-castor oil mixture. The granulated mixture is then tableted to form a plurality of slugs or cores 1 which are placed in a coating pan. The initial layer or coating 2 is formed by adding approxitrrately eight ounces of the glaze-stearic acid-castor oil mixture and thereupon dusting in approximately two pounds of powdered kaolin. This layer 2 can be built up gradually in a series of successive films if desired. After the layer 2 has been firmly applied, the coated slugs can be removed from the coating pan and allowed to dry for about twenty-four hours. Thereupon, the coated slugs are again placed in a coating pan and approximately eight to ten ounces of simple syrup USP are slowly powdered into the coating pan and the outer medicated layer 3 is formed by dusting in a quantity of powdered sodium phenobarbital in a quantity sufiioient to provide a one grain dosage in such outer layer .3. Finally, the outer sugar-coating layer 4 of any desired color may be formed by the addition of approximately twelve ounces of a conventional pharmaceutical sugarcoating liquid.

Formulated and manufactured as described in connection with Example I.

Example Ill Core:

Phenobarbital mg 30 Lactose (filler) gr 1 /2 Outer layer: Phenobarbital mg 30 Formulated and manufactured as described in connection with Example I.

It should be understood that changes and modifications in the form, construction, arrangement, and combination of the several parts of the pharmaceutical preparation may be made and substituted for those herein shown and described without departing from the nature and principle of my invention.

Having thus described my invention, what I claim and desire to secure by Letters Patent is:

l. The method of making a prolonged action medicinal tablet which comprises mixing a dry powdered drug material, confectioners glaze, stearic acid and castor oil to a dough-like consistency, spreading the mixture to dry and, when dry, comminuting to granulate the mixture to form discrete granules, mixing said granules with a composition consisting of confectioners glaze, stearic acid and castor oil to form a mixture of dough-like consistency, again spreading the latter dough-like mixture to dry and, when dry, comminuting same to form discrete granules, and compressing a measured quantity of the last-mentioned granules to form a solid tablet.

2. The method of making a prolonged action medicinal tablet which comprises mixing a dry powdered drug material, confectioners glaze, stearic acid and castor oil to a dough-like consistency, spreading the mixture to dry and, when dry, comminuting to granulate the mixture to form discrete granules, mixing said granules with a composition consisting of confectioners glaze, stearic acid and castor oil to form a mixture of dough-like consistency, again spreading the latter dough-like mixture to dry and, when dry, comminuting same to form discrete granules, screening said last-mentioned granules to produce a quantity of granules of substantially uniform size, and compressing a measured quantity of the lastmentioned granules to form a solid tablet.

3. The method of making a prolonged action medicinal tablet which comprises mixing a dry powdered drug material, confectioners glaze, stearic acid and castor oil to a dough-like consistency, spreading the mixture to dry and, when dry, comminuting to granulate the mixture to form discrete granules, screening the granules to produce a quantity of granules of substantially uniform size, mixing said granules with a composition consisting of confectioners glaze, stearic acid and castor oil to form a mixture of dough-like consistency, again spreading the latter dough-like mixture to dry and, when dry, comininuting smile to form discrete granules, screening said last-mentioned granules to produce a quantity of granules of substantially uniform size, and compressing a measured quantity of the last-mentioned granules to form a solid tablet.

4. The method of making a prolonged action sedative tablet which comprises mixing a dry sedative drug, confectioners glaze, stearic acid and castor oil to a doughlike consistency, spreading the mixture to dry and, when dry, comminuting to granulate the mixture to form discrete granules, mixing said granules with a composition consisting of confectioners glaze, stearic acid and castor oil to form a mixture of dough-like consistency, again spreading the latter dough-like mixture to dry and, when dry, comminuting same to form discrete granules, and compressing a measured quantity of the last-mentioned granules to form a solid tablet.

5. The method of forming a prolonged action sedative tablet which comprises mixing a dry sedative drug, confectioners glaze, stearic acid and castor oil to a doughlike consistency, spreading the mixture to dry and, when dry, comminuting to granulate the mixture to form discrete granules, screening the granules to produce a quantity of granules of substantially uniform size, mixing said granules with a composition consisting of confectioners glaze, stearic acid and castor oil to form a mixture of dough-like consistency, again spreading the latter doughlike mixture to dry and, when dry, comminuting same to form discrete granules, screening said last-mentioned granules to produce a quantity of granules of substantially uniform size, and compressing a measured quantity of the last-mentioned granules to form a solid tablet.

6. The method of making a prolonged action medicinal tablet which comprises mixing a dry powdered drug material, confectioners glaze, stearic acid and castor oil to a dough-like consistency, spreading the mixture to dry and, when dry, comminuting to granulate the mixture to form discrete granules, mixing said granules with a composition consisting of confectioners glaze, stearic acid and castor oil to form a mixture of dough-like consistency, again spreading the latter dough-like mixture to dry and, when dry, comminuting same to form discrete granules, compressing a measured quantity of the lastmentioned granules to form a solid tablet, enrobing said solid tablet in an enteric coating and drying said coating, thereupon wetting the outer surface of the enrobed tablet with a water-soluble excipient, applying a second dry powdered drug material upon the wetted tablet until same is again substantially dry to form an outer drug containing layer.

References Cited in the file of this patent UNITED STATES PATENTS 1,928,346 Axelrod Sept. 26, 1933 2,146,867 Welin Feb. 14, 1939 2,207,990 Miller July 16, 1940 2,373,763 Kuever Apr. 17, 1945 2,553,806 Bogin et al. May 22, 1951 2,566,200 Hickey Aug. 28, 1951 FOREIGN PATENTS 285,091 Great Britain June 10, 1929 OTHER REFERENCES Silver et al.: Mfg. of Compressed Tablets, Stokes Machine Co., 1944, pp. 11-20.

Di-Barbs, Chain Store Age, Drug Store Mgrs. Ed., sec. 1, June 1949. 

1. THE METHOD OF MAKING A PROLONGED ACTION MEDICINAL TABLET WHICH COMPRISES MIXING A DRY POWDERED DRUG MATERIAL, CONFECTIONERS'' GLAZE, STEARIC ACID AND CASTOR OIL TO A DOUGH-LIKE CONSISTENCY, SPREADING THE MIXTURE TO DRY AND, WHEN DRY, COMMINUTING TO GRANULATE THE MIXTURE TO FORM DISCRETE GRANULES, MIXING SAID GRANULES WITH A COMPOSITION CONSISTING OF CONFECTIONERS'' GLAZE, STEARIC ACID AND CASTOR OIL TO FORM A MIXTURE OF DOUGH-LIKE CONSISTENCY, AGAIN SPREADING A DOUGH-LIKE MIXTURE TO DRY AND, WHEN DRY, COMMINUTING SAME TO FORM DISCRETE GRANULES, AND COMPRESSING A MEASURED QUANTITY OF THE LAST-MENTIONED GRANULES TO FORM A SOLID TABLET. 